Welcome to 'Current Understanding of Immune Mechanisms.' The immune system is poised to distinguish self from foreign substances or non-self, as a first line of defense. This session will examine areas of biology and medicine of the human immune system's structure, cell involvement, and function—all of which impact states of health and disease.

Antigen-presenting cells process proteins into peptides for binding by either major histocompatibility class I (MHC-I) or class II (MHC-II) molecules which are then displayed at the cell surface as peptide/MHC complexes, where they are recognized by T cell receptors, leading to T cell activation. MHC-I molecules also serve as indispensable ligands for a variety of NK cell receptors. The cell-biological, biochemical, and structural details of these processes as we now understand them will be discussed, as well as recent data on strategies for human NK cell activation for cancer immunotherapy.

This presentation will overview the four areas of hypersensitivity: immediate Type I IgE-mediated, Type II antibody-dependent cytotoxicity, Type III immune-complex-mediated, and delayed-Type hypersensitivity. Type I human allergic disease will then be examined, covering its pathophysiology, current diagnostic strategies, four modes of disease management, and special caveats relating to food, drug, venom, and respiratory allergic disease. Finally, the new discipline of molecular allergology will be highlighted with an emphasis on ten cross-reactive allergen families and how allergenic molecules have improved the accuracy of allergy diagnosis.

This session will present an overview of immunogenicity risk assessment strategies for biotherapeutics, focusing on commonly applied in silico and in vitro tools. This talk will outline key concepts, standard workflows, and the strengths and limitations of current approaches. Emphasis will be placed on the role of these approaches in enabling informed decision-making during early-stage development.

Immune checkpoint inhibitors, bispecific antibodies, and antibody-drug conjugates have reshaped oncology, but each carries distinct and sometimes overlapping immunological safety risks. This presentation reviews major toxicity mechanisms, including loss of immune tolerance, cytokine release, effector-cell overactivation, and inflammatory tissue injury. Drawing on cross-modality case examples, it highlights how target biology, molecular format, payload properties, and dose schedules influence clinical safety outcomes. The session also discusses practical approaches to improving the therapeutic index, including translational nonclinical assessments, biomarker-guided monitoring, patient selection, and proactive clinical mitigation. Attendees will gain a concise framework for anticipating and managing immunological risk across these evolving platforms.

Antibody-based therapeutics have provided great therapeutic benefit to many patients across various disease states. Multispecific antibodies afford therapeutic opportunities not feasible with single-target antibodies or combinations, while drug conjugates provide the opportunity to extend therapeutic benefit through combining the targeting specificity of an antibody with a 'payload.' Examples of these advances will be summarized in the context of molecule design, target selection, biological characterization, and clinical benefit.

CD28 and 4-1BB are two indispensable costimulatory receptors on T cells playing key role in tumor immunity and my talk can help understand the risk and benefit of engaging CD28 and 4-1BB by agonistic antibodies. I will provide a comprehensive background on costimulatory receptors CD28 and 4-1BB and then dive deep into the mechanisms of actions by showing first hand data from innovative in vitro assay platforms.

While it has long been appreciated that liver-derived systemic complement guards the vascular space, it has been more recently recognized that cell-intrinsic and/or intracellularly derived complement components play pivotal roles in tissue immunity through the regulation of normal cell physiology, metabolism, survival, and effector functions in a plethora of cell types in the human body. Our lab studies the role of cell-autonomous complement in immune and non-immune cells and its function in homeostasis and disease (infection, cancer, and autoimmunity) to further our understanding of how this system can be targeted therapeutically.

Understanding the immunogenicity of biopharmaceuticals is essential to ongoing product development, clinical use, and regulatory approval. Numerous risk factors may provoke immune responses, potentially reducing efficacy and, in some cases, leading to safety concerns such as hypersensitivity reactions, immune complex syndromes, and autoimmune disorders. This overview examines the factors influencing immune responses to biotherapeutics, the clinical impact of unwanted immunogenicity, and mitigation strategies to improve patient outcomes.